The ability of low concentrations of fluoride ions to protect teeth against the development of carious lesions is well known. However, the mechanism by which the protective effect is exerted still is only poorly understood. Two hypotheses have been put forward to explain the findings. The first related the protective action to the increased stability of the enamel to acid as a result of the incorporation of fluoride into the apatite lattice. The second deals with the ability of fluoride to interfere with the acid-producing capacities of plaque organisms. Our studies have confirmed the inhibitory capacity of even 1 ppm of fluorine. However, different plaque-derived organisms exhibit widely divergent sensitivities to the anion. One such microorganism has been found to take up fluoride intracellularly and to concentrate it in two distinct compartments. The goals of the proposed investigation are to examine fluoride uptake in order to determine which of the compartments contains metabolically active fluoride and to try to correlate uptake and binding processes with susceptibility to fluoride in different microorganisms. An appreciation of these mechanisms may lead to improvements in the effective delivery of fluoride for therapeutic purposes.